Sugar Coating Works for Nanoparticles

Raising the temperature of human tissue by as little as 5oC damages or kills cells, and thermal ablation offers an alternative to chemotherapy or radiotherapy for the treatment of cancer. The main challenge in the clinical application of thermal therapy is how to selectively cause necrosis within a tumour, without overheating and damaging surrounding tissue. Magnetic nanoparticles, particularly if they can be targeted selectively to a tumour, offer the potential to deliver heat in a site-selective, and even cell-selective, manner. Nanoparticles for biomedical applications are most often formed using magnetite (Fe3O4) and their manufacture requires the synthesis of stable colloidal suspensions in biocompatible fluids (water or saline) that maintain their stability in blood or plasma. The particles must also produce a predictable and sufficient amount of heat when modest particle concentrations are exposed to alternating magnetic fields at amplitudes that can be applied safely to large areas of tissue. These criteria mean that the surface chemistry, size, and magnetic properties of the particles must be tightly controlled during manufacture.

Many scientists had believed that the best results would be achieved with small, non-interacting particles which can evade the body’s immune system, but a study led by researchers at the National Institute of Standards and Technology (NIST) has shown that dextran-coated magnetic particles that have good in vivo efficacy interact strongly with each other. In a mouse breast cancer model, three out of four mice treated with a single dose of the particles displayed a complete response, with no tumour re-growth during the 60 day study period. To produce the particles, a dextran shell was physically adsorbed onto an iron oxide core, giving particles with a diameter (core + shell) of ca 100nM. Extensive characterisation of the particles revealed a preferred interparticle spacing, consistent with chain-forming interactions between the particles. Although the magnetic cores of the particles attract each other, fibres from the dextran coat prevent the particles from clumping together and eliciting an immune response. When ingested by tumour cells, the association between the particles is close enough to increase their heat-generating efficiency when subjected to an alternating magnetic field.

An iron-centered nanoparticle (left) analyzed at NIST's Center for Neutron Research has a coating of the sugar dextran, whose tendrils prevent groups of the particles from clumping. When tumour cells ingest them (right), the particles still congregate closely enough to share heat when stimulated by a magnetic field, killing the cells. White arrow indicates a red blood cell. Credit: NIST

The findings, which are published in the journal Nanotechnology, may help in the design of better nanoparticles for the treatment of cancer.